Raili Raininko

Low back pain in relation to lumbar disc degeneration

STUDY DESIGN Cross-sectional magnetic resonance imaging (MRI) study. OBJECTIVES To study the relation of low back pain (LBP) to disc degeneration in the lumbar spine. BACKGROUND DATA Controversy still prevails about the relationship between disc degeneration and LBP. Classification of disc degeneration and symptoms varies, hampering comparison of study results. METHODS Subjects comprised 164 men aged 40-45 years-53 machine drivers, 51 construction carpenters, and 60 office workers. The data of different types of LBP, individual characteristics, and lifestyle factors were obtained from a questionnaire and a structured interview. Degeneration of discs L2/L3-L5/S1 (dark nucleus pulposus and posterior and anterior bulge) was assessed with MRI. RESULTS An increased risk of LBP (including all types) was found in relation to all signs of disc degeneration. An increased risk of sciatic pain was found in relation to posterior bulges, but local LBP was not related to disc degeneration. The risks of LBP and sciatic pain were strongly affected by occupation. CONCLUSIONS Low back pain is associated with signs of disc degeneration and sciatic pain with posterior disc bulges. Low back pain is strongly associated with occupation.

White Matter Hyperintensities on MRI in the Neurologically Nondiseased Elderly: Analysis of Cohorts of Consecutive Subjects Aged 55 to 85 Years Living at Home

BACKGROUND AND PURPOSE We undertook this study to evaluate the frequency and risk factors of white matter hyperintensities seen on T2-weighted MR imaging. We examined cohorts of neurologically nondiseased elderly subjects participating in a general-community study, the Helsinki (Finland) Aging Brain Study. Cohorts of consecutive subjects aged 55, 60, 65, 70, 75, 80, and 85 years (n = 20, 18, 20, 18, 19, 18, and 15, respectively; total, n = 128) were divided into a young-old (age < 75 years, n = 76) group and an old-old (age > or = 75 years, n = 52) group. METHODS Frequency of hyperintensities seen on T2-weighted axial and coronal MR images (0.02 T) was rated using a four-point scale in periventricular and centrum semiovale areas. RESULTS The majority of the subjects showed only mild white matter hyperintensities, which were more frequent in the periventricular areas. Age was the most important factor to explain the presence of hyperintensities. A logistic regression analysis related periventricular hyperintensities in the entire group to central atrophy (odds ratio [OR], 4.7; 95% confidence interval [CI], 1.7 to 12.9) and silent infarcts (OR, 5.6; 95% CI, 1.0 to 19.8); among the young-old, hyperintensities related to diabetes (OR, 17.0; 95% CI, 1.9 to 154.2) and central atrophy (OR, 14.7; 95% CI, 3.5 to 61.8). Centrum semiovale hyperintensities related in the entire group to cardiac arrhythmia (OR, 4.0; 95% CI, 1.0 to 15.5), central atrophy (OR, 3.9; 95% CI, 1.2 to 12.4), and silent infarcts (OR, 3.6; 95% CI, 1.0 to 12.5). CONCLUSIONS These mild white matter hyperintensities in the neurologically nondiseased elderly related especially to age and also to concomitant silent infarcts, atrophy, and some vascular risk factors. The known factors, however, explained only part of the variation. The young-old and old-old groups showed different associations. In contrast to former assumptions, the presence of white matter hyperintensities among the aged is likely to be linked to other as yet unidentified age-related factors.

Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is associated with dementia.

ObjectiveTo relate the expression of HIV regulatory proteins and HIV-specific mRNA in the brain cells of infected individuals with clinical neurological disease. DesignFormalin-fixed postmortem brain tissue from 14 HIV-infected adult patients, with previous repeated neurological and neuroradiological examinations, was studied by immunohistochemical and molecular biological methods. Samples from non-infected brains served as controls. MethodsImmunohistochemistry with monoclonal antibodies (MAb) was combined with in situ RNA hybridization. Target cells were identified with MAb to glial fibrillary acidic protein (GFAP; astrocytes), CD68 (activated macrophages) and Ricinus communis agglutinin (RCA-1; microglia, endothelial cells). For HIV, a panel of MAb against HIV Nef, Tat, Rev and Env proteins or probes specific for all classes of mRNA (net), for singly or non-spliced mRNA (env) and for non-spliced mRNA (gag/pot) were used. ResultsNef protein was detected in subcortical or subpial astrocytes in seven out of 14 samples, and in multinucleated giant cells in two cases. Gag/pol or env mRNA-expressing astrocytes were detected in four cases. In four out of five cases studied, HIV Rev, but not Tat, was also expressed in astrocytes. Six out of the seven patients with Nef-positive astrocytes had suffered from moderate to severe dementia. The patient with most rapidly progressing severe dementia showed extensive HIV mRNA expression together with Nef and Rev expression in astrocytes. ConclusionIn adult human brain, astrocytes are infected by HIV and preferentially express HIV Nef and Rev proteins but are also sometimes productively infected. Astrocyte infection is associated with moderate to severe dementia which agrees with recent knowledge on the housekeeping activities of astrocytes and their eventual role in learning and memory.

Possible association of interleukin 1 gene locus polymorphisms with low back pain

&NA; Based on a hypothesis that interleukin 1 (IL‐1) activity is associated with low back pain (LBP), we investigated relationships between previously described functional IL‐1 gene polymorphisms and LBP. The subjects were a subgroup of a Finnish study cohort. The IL‐1&agr;(C889–T), IL‐1&bgr;(C3954–T) and IL‐1 receptor antagonist (IL‐1RN)(G1812–A, G1887–C and T11100–C) polymorphisms were genotyped in 131 middle‐aged men from three occupational groups (machine drivers, carpenters and office workers). A questionnaire inquired about individual and lifestyle characteristics and the occurrence of LBP, the number of days with pain and days with limitation of daily activities because of pain, and pain intensity, during the past 12 months. Lumbar disc degeneration was determined with magnetic resonance imaging. Carriers of the IL‐1RNA1812 allele had an increased risk of LBP (OR 2.5, 95% CI 1.0–6.0) and carriers of this allele in combination with the IL‐1&agr;T889 or IL‐1&bgr;T3954 allele had a higher risk of and more days with LBP than non‐carriers. Pain intensity was associated with the simultaneous carriage of the IL‐1&agr;T889 and IL‐1RNA1812 alleles (OR 3.7, 95% CI 1.2–11.9). Multiple regression analyses allowing for occupation and disc degeneration showed that carriage of the IL‐1RNA1812 allele was associated with the occurrence of pain, the number of days with pain and days with limitations of daily activities. Carriage of the IL‐1&bgr;T3954 allele was associated with the number of days with pain. The results suggest a possible contribution of the IL‐1 gene locus polymorphisms to the pathogenesis of LBP. The possibility of chance findings cannot be excluded due to the small sample size.

Interleukin 1 polymorphisms and intervertebral disc degeneration.

Background: Enzymatic breakdown of the extracellular matrix, and possibly local inflammation, contributes to intervertebral disc degeneration. We investigated whether polymorphisms within the IL-1 gene locus are associated with lumbar disc degeneration and whether the effect of occupational physical load on disc degeneration is modified by the polymorphisms. Methods: Genotypes were determined from 133 middle-aged men who underwent magnetic resonance imaging of the lumbar spine. The participants represented 3 occupations: 40 were machine drivers, 42 carpenters, and 51 office workers. We evaluated decreased signal intensity of the nucleus pulposus, disc bulges, and decreased disc height as signs of degeneration in the L2/L3–L5/S1 discs. Results: The odds ratio for disc bulges was 2.4 (95% confidence interval = 1.2– 4.8) and 1.9 (1.0–3.7), in carriers of the IL-1αT889 or IL-1βT3954 alleles, respectively. The TT genotype of the IL-1α gene carried more than 3-fold risk of disc bulges as compared with the CC genotype. Conclusions: IL-1 gene cluster polymorphisms could affect the risk of disc degeneration. The effect of physical workload seems to be modified by the IL-1 gene polymorphisms.

Disc height and signal intensity of the nucleus pulposus on magnetic resonance imaging as indicators of lumbar disc degeneration.

Study Design. A cross-sectional magnetic resonance imaging (MRI) study of degeneration of the lumbar spine. Objectives. To compare the usefulness of disc height and that of T2-weighted signal intensity as indicators of disc degeneration. Summary of Background Data. Disc height and signal intensity have been used as indicators for disc degeneration. Their relation to each other and to early degeneration has not been well documented. There is evidence that physical load can affect disc height. Methods. Forty-one machine operators, 41 construction carpenters, and 46 office workers, aged 40–45 years, and 22 students aged 18–20 years were examined with sagittal magnetic resonance imaging. All study participants were men. The mean value of the anterior and posterior disc height and the relative T2-weighted signal intensity of the nucleus pulposus of discs L2–L3 to L5–S1 were measured. Results. Young men showed the lowest disc height but the highest relative signal intensity. Disc height showed an increasing trend from the office workers (sedentary) to blue-collar workers (more physical work) at all disc levels but L5–S1. Relative signal intensity showed a decreasing trend for these same worker types at all levels. In generalized linear modeling, signal intensity and the occupations, in reference to the young students, showed a significant effect on disc height. Conclusions. Relative signal intensity was lower in the middle-aged men than in the young men, indicating age-related disc degeneration. Despite the general positive association between disc narrowing and decreased relative signal intensity, disc narrowing may behave unexpectedly in relation to signal intensity and age. Signal intensity may be a more sensitive measure of disc degeneration. The validity of disc height as an indicator of early degeneration seems questionable.

Lumbosacral transitional vertebra: relation to disc degeneration and low back pain.

Study Design. Cross-sectional magnetic-resonance imaging (MRI) study. Objective. To investigate the relation of the lumbosacral transitional vertebra to signs of disc degeneration in MRI and to low back pain (LBP). Summary of Background Data. An association between the transitional vertebra and herniation in the disc above has been found in patients with LBP, but knowledge of the relation to other degenerative disc changes detected in MRI and to LBP is lacking. Methods. MR images of the lumbar spine of 138 middle-aged working men and 25 healthy young men were evaluated. The presence and type of lumbosacral transitional vertebra and of degenerative changes in intervertebral discs were evaluated. The history of low back symptoms was obtained with a questionnaire from the middle-aged men. Results. The prevalence of transitional vertebra was 30%. Transitional vertebra was associated with an increased risk of degenerative changes in the disc above among the young men and with a decreased risk in the disc below among the middle-aged men. Transitional vertebra, symmetric or asymmetric, was not associated with any type of LBP in the middle-aged men. Conclusions. Lumbosacral transitional vertebra increases the risk of early degeneration in the upper disc. This effect seems to be obscured by age-related changes in the middle age. The degenerative process is slowed down in the lower disc. For these effects, the presence of a transitional vertebra should be noticed when morphologic methods are used in research on lumbosacral spine. Transitional vertebra is not associated with any type of LBP.

Childhood epilepsy, familial hemiplegic migraine, cerebellar ataxia, and a new CACNA1A mutation.

The CACNA1A gene encodes the pore-forming subunit of neuronal P/Q type Ca2+ channels. Mutations in this gene cause a spectrum of neurologic diseases, including familial hemiplegic migraine (FHM) with or without ataxia.1 We report a novel de novo CACNA1A mutation in a Swedish family. Three mutation carriers had FHM and early onset ataxia; additional childhood epilepsy occurred in two . The proband, II-3, is a 54-year-old woman with slowly progressive cerebellar ataxia since childhood and cerebellar atrophy on CT. She was hospitalized at ages 7 and 8 because of decreased consciousness and vomiting for 1 day, starting with a lucid interval after a fall. She experienced four hemiplegic migraine attacks between ages 14 and 30 years and weekly at age 47. Seizures were never observed. Her 32-year-old son (III-5) and 30-year-old daughter (III-6), who have different fathers, showed cerebellar ataxia at age 4. Ataxia is now prominent in both, and brain imaging shows cerebellar atrophy. …

Observer variability in the assessment of disc degeneration on magnetic resonance images of the lumbar and thoracic spine

Study Design. Intraobserver and interobserver reproducibility study. Objective. This study investigates the variability in the interpretation of degenerative disc findings using magnetic resonance imaging. Summary of Background Data. Magnetic resonance imaging has been used for years in clinical diagnostics, primarily to investigate disc herniation and spinal stenosis. Less attention has been paid to other disc findings and their assessment reliability. Methods. Three independent readers evaluated magnetic resonance images of the lumbar and the lower and middle thoracic spines of 122 subjects by grading 12 aspects of the intervertebral discs and adjacent endplates using written definitions and example images. Images of 20 subjects were reevaluated for the assessment of intraobserver agreement. Results. Agreement was highest in the lower lumbar and poorest in the middle thoracic spine. Intraobserver agreement was generally fair to excellent for almost all variables in the lumbar and lower thoracic spine (most intraclass correlation and kappa coefficients for these regions were above 0.70). Interobserver agreement was notably lower than intraobserver agreement, except for osteophytes and endplate defects in some regions. Conclusions. Intraobserver agreement in the evaluation of disc degeneration was at an acceptable level, in general, in the lumbar and lower thoracic spine. However, assessments were substantially more variable between readers, which limits comparisons of evaluations between different readers.

Intervertebral disc degeneration in relation to the COL9A3 and the IL-1ß gene polymorphisms

Disc degeneration is a complex condition in which environmental factors and multiple genes are expected to act together to determine the degenerative phenotype. Recently associations of COL9A2 (Trp2 allele) and COL9A3 (Trp3 allele) polymorphisms with lumbar disc disease characterized by sciatica have been reported. However, it is not known whether the Trp2 or Trp3 alleles contribute to disc degeneration (DD). In this study, the association between the collagen genes polymorphisms and lumbar DD was investigated. Furthermore, the influence of the IL-1β(C3954-T) polymorphism on the association of collagen genes polymorphisms with DD was examined. Lumbar intervertebral discs of 135 middle-aged occupationally active men were evaluated with magnetic resonance imaging, using decreased signal intensity of the nucleus pulposus, disc bulges, and decreased disc height as signs of degeneration. Blood samples were analysed for the presence of COL9A3 and COL9A2 tryptophan alleles (Trp3 and Trp2 alleles). The COL11A2, COL2A1 and IL-1β(C3954-T) polymorphisms were also analysed. Multivariate logistic regression analysis allowing for occupation and body mass index showed that the carriage of the Trp3 allele in the absence of the IL-1βT3954 allele increased the risk of dark nucleus pulposus (OR 7.0, 95% CI 1.3–38.8) and joint occurrence of degenerative changes (OR 8.0, 95% CI 1.4–44.7). There was no effect of the Trp3 allele on DD in the presence of the IL-1βT3954 allele. The carriers of the COL11A2 minor allele had an increased risk of disc bulges (OR 2.1, 95% CI 1.0–4.2) as compared with non-carriers. The results suggest that the effect of the COL9A3 gene polymorphism on DD might be modified by the IL-1β gene polymorphism.